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Cell cycle: proliferation, maturation and apoptosis
Lecture Details Jeff Kerr; Week 3 MED1011; Anatomy Lecture Content Skin is replaced every 4 weeks, hair constantly grows, liver cells once a year, blood vessel walls can be replaced in days, heart tissue and nerves are not replaceable, gut epithelial cells can be replaced every 4-5 days, uterus muscle multiplies in pregnancy, bone marrow makes millions of cells a second. Stem cells in gut make Paneth cells in crypt, goblet cells, enteroendocrine cells and enterocytes on the villus. The gut loses 1400 cells per villus a day. The cell cycle has interphase (nondividing) and mitosis (dividing). The cycle is divided by checkpoints. Mitosis is subdivided into 5 stages (metaphase, prophase, metaphase, anaphase, telophase, cytokinesis). The liver regenerates by mitosis. Muscle satellite cells are reserve cells, and are usually quiescent but after injury or exercise, contribute to muscle regeneration. The cell cycle has M phase (mitosis) the interphase through G1 (gap), S phase (DNA replication) and G2 (gap) phase. G0 is when the cell exits from cycle and is at rest. It might be stimulated to divide (regenerating liver) from this phase. Checkpoints prevent entry into next phase until preceding phase events are complete. There is a G1 checkpoint for damaged DNA, an S checkpoint for unreplicated or damaged DNA, a G2 checkpoint for unreplicated or damaged DNA and an M checkpoint for chromosome misalignment. The molecules that checkpoint are protein kinases that phosphorylate proteins to switch on or off activity. Cyclins switch kinases on or off. Kinases are cyclin-dependant protein kinases (Cdks). Cyclins and Cdks rise and fall in activity over the cell cycle. During mitosis, chromosomes condense, nuclear envelope breaks down, cytoskeleton rearranges to mitotic spindle and chromosomes move to opposite poles. Prophase is appearance of condensed chromosomes and development of mitotic spindle. Metaphase is where chromosomes are aligned on a metaphase plate in the centre of the cell. Anaphase is where sister chromatids separate to poles of the spindle. Telophase is where nuclei reform and chromosomes decondense. Cytokinesis is where there is invagination down the centre of the cells and they split. Apoptosis is used to shape fingers, needless tails/other structures on animals. Apoptosis is genetically regulated. It is required in gut epithelium, uterine glands, liver, germ cells, WBC, blood/bone marrow. Tumour suppressor genes, if mutated, can lead to cancer. p53 is one gene that over 50% of cancers develop from. p53 arrests the cell cycle and induces apoptosis. Without p53 there is 100% cancer incidence. p53 mutants can be heritable (Li-Fraumeni cancer disposition syndrome). It is involved in longevity, neural-tube closure, differentiation, fertility, pigmentation, homeostasis. p63 and 73 are also part of the family. Accidental cell injury is necrosis. Cells swell and burst, with debris causing inflammation. Caspase zymogens have to be activated by genes to form caspases. Caspase enzymes are the executioners of apoptosis. Without caspase there is too much tissue. Tail resorption is mediated by T3, first part is apoptosis, second is phagocytes. Readings Life (8th); 184-192, 202-203